Punctuated evolution of prostate cancer genomes.

TitlePunctuated evolution of prostate cancer genomes.
Publication TypeJournal Article
Year of Publication2013
AuthorsBaca SC, Prandi D, Lawrence MS, Mosquera JMiguel, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat J-P, T Soong D, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA
JournalCell
Volume153
Issue3
Pagination666-77
Date Published2013 Apr 25
ISSN1097-4172
KeywordsAdenocarcinoma, Chromosome Aberrations, Cohort Studies, Gene Expression Regulation, Neoplastic, Genome, Human, Genome-Wide Association Study, Humans, Male, Neuroendocrine Tumors, Prostatic Neoplasms
Abstract

The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term "chromoplexy," frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis.

DOI10.1016/j.cell.2013.03.021
Alternate JournalCell
PubMed ID23622249
PubMed Central IDPMC3690918
Grant ListP50 CA090381 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
U01 CA162148 / CA / NCI NIH HHS / United States
R01 CA125612 / CA / NCI NIH HHS / United States
DP2OD002750 / OD / NIH HHS / United States
DP2 OD002750 / OD / NIH HHS / United States
R33 CA155554 / CA / NCI NIH HHS / United States
U01CA111275 / CA / NCI NIH HHS / United States
T32GM007753 / GM / NIGMS NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States